Scale-up and Manufacturing of STLR-201, an off-the-shelf regenerative therapeutic for Sjogren's syndrome-related dry eye disease

PROJECT SUMMARY: Sjogren’s syndrome-related dry eye (SSDE), affects about two million people in the U.S. and arises from an autoimmune disorder that damages the lacrimal glands. A cascade of pathological changes perpetuates and advances corneal damage, resulting in pain, blurred vision, and photosensitivity that makes it difficult to perform daily functions, resulting in reduced work productivity and a greatly reduced quality of life. Most therapies only temporarily treat symptoms, and the underlying SSDE can continue to progress. In addition, some treatments are slow to take effect and have side effects, making them less appealing to patients. Several disease-modifying therapies have shown promise against dry eye disease in general, including autologous blood products; however, these autologous products are patient-specific, requiring individualized manufacturing that lacks product characterization or quality control and are not covered by insurance. Therefore, there is a critical unmet need for an off-the-shelf, fast-acting, disease-modifying SSDE therapy. Stellular Bio has harnessed the power of platelet and stem cell biology to produce an off-the-shelf SSDE therapeutic. Their proprietary platform enables the differentiation of induced pluripotent stem cells into platelet precursor megakaryocyte-like cells (MLCs) to generate an MLC extract containing a unique blend of growth factors and cytokines known to stimulate corneal epithelial and neuronal cell growth and reduce immune cell-mediated cell loss. This MLC extract, being iPSC-derived, makes for a quality-controlled, allogeneic, ocular product with a renewable cell source. Stellular Bio's therapeutic candidate, STLR-201, promotes corneal epithelial cell proliferation in vitro and significantly improves corneal barrier integrity in dry eye disease mouse models in two weeks, with effects persisting at least two weeks post-treatment. Thus, STLR-201 represents a promising SSDE therapeutic. This SBIR Fast-Track project will finalize the STLR-201 drug substance processing strategy and scale up production and GMP manu- facturing to support chemistry, manufacturing, and control (CMC) and GLP toxicology studies, which will be accomplished with the following specific aims: Phase I – 1) Finalize drug substance processing strategy and scale up to enable processing of MLCs from a full-size manufacturing run; 2) Determine comparability of new pilot process and proof-of-concept product, including in vitro and in vivo bioactivity; Phase II – 1) Process devel- opment: production of MLCs by stirred bioreactor culture, establishing a scalable, more efficient, cost-effective manufacturing method; 2) Perform engineering runs of final STLR-201 production process, including variability testing and generating product for IND-enabling studies; 3) Perform STLR-201 GMP manufacturing run, includ- ing defining release criteria, generating GMP product, and evaluating stability. Project success will generate an optimized GMP STLR-201 manufacturing process and critical CMC data to support IND submission and clinical trials. STLR-201 is poised to be the first FDA-approved off-the-shelf regenerative SSDE treatment that can stop disease progression and restore cornea integrity, providing life-changing outcomes for SSDE patients.